Blueprint Medicines Corp (BPMC) 2025 Q1 法說會逐字稿

Good morning. My name is Angela Lang, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines first-Q 2025 earnings release and conference call. (Operator Instructions)

早安.我叫安琪拉‧朗 (Angela Lang)，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Blueprint Medicines 2025 年第一季財報發表會和電話會議。（操作員指示）

Thank you. Jenna Cohen, you may begin your conference.

謝謝。詹娜·科恩，你可以開始你的會議了。

Thank you, Angela. Good morning, everyone, and welcome to Blueprint Medicines first quarter 2025 financial and operating results conference call. This morning we issued a press release which outlines the topics we plan to discuss today. You can access the press release as well as the slides that we'll be reviewing today by going to the Investor section of our website at www.Blueprintmedicines.com.

謝謝你，安吉拉。大家早安，歡迎參加 Blueprint Medicines 2025 年第一季財務與經營業績電話會議。今天早上我們發布了一份新聞稿，概述了我們今天計劃討論的話題。您可以透過造訪我們網站 www.Blueprintmedicines.com 的投資者部分來存取新聞稿以及我們今天將要審查的幻燈片。

Joining me today are Kate Haviland, Chief Executive Officer; Philina Lee, Chief Commercial Officer; Becker Hewes, Chief Medical Officer; and Mike Landsittel, Chief Financial Officer. Fouad Namouni, President of Research and Development; and Christy Rossi, Chief Operating Officer are also on the line and available for Q&A.

今天與我一起出席的還有首席執行官 Kate Haviland； Philina Lee，首席商務官； Becker Hewes，首席醫療官；以及首席財務官 Mike Landsittel。研發總裁 Fouad Namouni；營運長 Christy Rossi 也在線，可以回答您的問題。

Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements as outlined on slide 3 and are subject to a number of risks and uncertainties. These may cause our actual results to differ materially, including those described in our reports filed with the SEC. You're cautioned not to place any undue reliance on these forward-looking statements and Blueprint disclaims any obligation to update such statements.

在我們開始之前，我想提醒您，今天電話會議中所做的某些陳述是前瞻性陳述，如幻燈片 3 中所述，並且受許多風險和不確定性的影響。這些可能會導致我們的實際結果大不相同，包括我們向美國證券交易委員會提交的報告中所述的結果。請注意不要過度依賴這些前瞻性陳述，Blueprint 不承擔更新此類陳述的任何義務。

I'll now hand the call over to Kate.

我現在將電話交給凱特。

Thank you, Jenna, and good morning, everyone. We at Blueprint Medicine strive to be a standout top tier biotech company with a core focus on innovation, commercial excellence and maintaining a durable financial profile that enables disciplined global investment across our portfolio.

謝謝你，珍娜，大家早安。Blueprint Medicine 致力於成為一家傑出的頂級生物技術公司，核心重點是創新、商業卓越和維持持久的財務狀況，從而能夠在我們的投資組合中進行有紀律的全球投資。

Following strong performance in 2024, we've continued our executionable momentum in 2025. This quarter, we achieved 61% year over year AYVAKIT revenue growth, as we continue to capture the substantial and growing multi billion dollar commercial opportunity and systemic mastocytosis, which we expect will drive our global revenue growth well into the next decade.

繼 2024 年取得強勁表現後，我們在 2025 年繼續保持可執行的勢頭。本季度，AYVAKIT 營收年增 61%，因為我們繼續抓住數十億美元的巨大且不斷增長的商業機會和系統性肥大細胞增多症，我們預計這將推動我們未來十年的全球收入成長。

With every additional quarter of performance, AYVAKIT progresses on the path to our goal of $2 billion in revenue by 2030. The underlying fundamental demand, driven by growth and patients on therapy is the critical determinant of long-term revenue potential, and we are pleased that our results in Q1 reflect continued strength in this metric as we expected.

隨著每季的業績成長，AYVAKIT 都在朝著 2030 年實現 20 億美元營收的目標邁進。由成長和接受治療的患者所驅動的潛在基本需求是長期收入潛力的關鍵決定因素，我們很高興看到第一季度的業績反映出這一指標的持續強勁，正如我們預期的那樣。

This strong fundamental growth coupled with significant favorability in our free versus paid good mix is leading us to raise our revenue guidance for the year. Philina will go into this more specifically in a moment. We also advanced our industry-leading pipeline of mass cell-directed investigational medicines.

強勁的基本成長加上免費商品與付費商品組合的顯著優勢，促使我們提高了今年的營收預期。Philina 稍後會更具體地討論這一點。我們也推進了業界領先的大規模細胞導向研究藥物管道。

Our two prioritized pipeline programs, elenestinib and BLU-808 have the potential to drive significant upside value for Blueprint as they progress in the clinic this year and beyond. With BLU-808, our wide type kit inhibitor, our goal is to raise the bar on what a treatment for a wide range of allergic and inflammatory diseases can offer by considering the full patient experience, efficacy, tolerability and the burden associated with administration.

我們的兩個優先管線項目 elenestinib 和 BLU-808 有可能在今年及以後的臨床研究中為 Blueprint 帶來巨大的上升價值。利用我們的廣譜試劑盒抑制劑 BLU-808，我們的目標是透過考慮患者的全面體驗、療效、耐受性和與給藥相關的負擔，提高多種過敏和發炎疾病的治療標準。

BLU-808's early clinical profile supports our differentiated approach to development, allowing us to explore a range of doses as well as dose regimens. As we announced this morning, BLU-808 has achieved key milestones with the initiation of two proof-of-concept studies, one in allergic rhinoconjunctivitis and one in chronic urticaria. We hope to be able to share some early data this year from these studies, which Becker will talk more about later on the call.

BLU-808 的早期臨床概況支持我們差異化的開發方法，使我們能夠探索一系列劑量以及劑量方案。正如我們今天早上宣布的那樣，BLU-808 已經取得了關鍵的里程碑，啟動了兩項概念驗證研究，一項針對過敏性鼻結膜炎，另一項針對慢性蕁麻疹。我們希望今年能夠分享這些研究的一些早期數據，貝克爾稍後將在電話會議上詳細討論。

Elenestinib, our next generation Kit D816V inhibitor has the potential best in disease profile that builds on our years of experience in SM. Given the strong receptivity of AYVAKIT by both physicians and patients, we know it is not enough to incrementally innovate with a follow-on medicine that will enter the market years after AYVAKIT.

Elenestinib 是我們下一代 Kit D816V 抑制劑，基於我們在 SM 領域累積多年的經驗，具有治療多種疾病的潛力。鑑於醫生和患者對 AYVAKIT 的強烈接受度，我們知道，僅僅對 AYVAKIT 上市數年後進入市場的後續藥物進行漸進式創新是不夠的。

With the pivotal HARBOR study up and running, we have a plan to deliver substantially differentiated and meaningful innovation with elenestinib that goes beyond symptomatic control to measures of organ healing and disease modification.

隨著關鍵的 HARBOR 研究的啟動和運行，我們計劃利用 elenestinib 實現實質的差異化和有意義的創新，超越症狀控制，達到器官癒合和疾病改變的措施。

Blueprint's durable commercial growth profile, strong cash position and disciplined capital allocation strategy afford us the ability to focus on executing our business to plan despite the broader market volatility (technical difficulty) improve every day.

Blueprint 持久的商業成長狀況、強勁的現金狀況和嚴謹的資本配置策略使我們能夠專注於按照計劃執行業務，儘管更廣泛的市場波動（技術難度）每天都在增加。

With that, I will turn it to Philina to discuss the quarter's commercial performance in more depth.

接下來，我將請 Philina 更深入地討論本季的商業表現。

Thanks, Kate. In the first quarter, we achieved $149.4 million in AYVAKIT global net product revenues with $129.4 million in the US and $20 million ex-US. Our strong commercial execution drove revenue growth in what we expected to be a challenging quarter due to the typical Q1 financial headwinds inherent in our industry.

謝謝，凱特。第一季度，AYVAKIT 全球淨產品收入達 1.494 億美元，其中美國市場收入 1.294 億美元，美國以外市場收入 0.20 億美元。由於我們行業固有的典型第一季財務逆風，我們預計這將是一個充滿挑戰的季度，但我們強大的商業執行力推動了營收成長。

Let's walk through the headwinds and tailwinds. The short-term financial headwinds we've discussed previously played out as we expected, including typical first quarter insurance dynamics impacting gross to net and the impact of fewer ordering days. With our growing base of business, these factors can have a meaningful impact on a quarter.

讓我們一起經歷逆風和順風。我們之前討論過的短期財務逆風正如我們預期的那樣，包括典型的第一季保險動態影響總收入與淨收入，以及訂購天數減少的影響。隨著我們業務基礎的不斷擴大，這些因素可能會對季度產生重大影響。

As Kate mentioned, fundamental demand growth driven by a growing number of patients on therapy is a critical determinant of long-term revenue potential. This is the function of more patients starting and staying on therapy. We're pleased that Q1 met our expectations as we saw growth in new patient starts, both in the US and in our international business.

正如凱特所提到的，接受治療的患者數量不斷增加所推動的基本需求成長是長期收入潛力的關鍵決定因素。這是更多患者開始並堅持治療的作用。我們很高興第一季達到了我們的預期，因為我們看到美國和國際業務的新患者數量都在增加。

Discontinuation rates remained low, and we continue to see encouraging trends towards multi-year duration of therapy in both advanced SM and ISM. A key variable we were watching this quarter was our mix of free versus commercial goods, as we managed through the Q1 reauthorization process and monitored the impact of the Part D redesign and foundation funding availability.

停藥率仍然很低，我們繼續看到晚期 SM 和 ISM 的多年治療持續趨勢令人鼓舞。本季我們關注的一個關鍵變數是免費商品與商業商品的組合，因為我們通過了 Q1 重新授權流程，並監控了 D 部分重新設計和基金會資金可用性的影響。

This played out more favorably than we expected with our free goods rate now well below 10%. As a result of these favorable dynamics today, we are raising our guidance range to $700 million to $720 million for the year. We are exactly where we want to be at this point in the year, and we're well positioned to drive growth through the rest of 2025 and beyond.

結果比我們預期的要好，我們的免費商品率現在遠低於 10%。由於今天這些有利的動態，我們將今年的指導範圍上調至 7 億至 7.2 億美元。我們正處於今年的預期目標，並且已準備好在 2025 年剩餘時間及以後推動成長。

We have a clear view of the SM opportunity in front of us as we move further down the path towards $2 billion in AYVAKIT revenue by 2030 and a $4 billion peak SM franchise opportunity. SM diagnoses are increasing globally, and with approximately 25,000 diagnosed SM patients in the US. We know we're in the early innings of market penetration.

我們清楚地看到了擺在我們面前的 SM 機遇，我們正朝著 2030 年 AYVAKIT 收入達到 20 億美元和 SM 特許經營機會達到 40 億美元的峰值的目標邁進。全球範圍內 SM 診斷數量正在增加，美國約有 25,000 名 SM 患者。我們知道我們正處於市場滲透的早期階段。

Roughly 20% penetration of currently diagnosed patients in the US alone gets it to $2 billion in annual revenue. We expect to grow new patients starts through the end of the year and beyond. Of course, it all starts with the right medicine, AYVAKIT, an effective therapy with a broad label that addresses the root cause of disease and is also very well tolerated, enabling patients to start and stay on therapy over the long term.

光是在美國，目前確診患者的滲透率約為 20%，每年的收入就達到 20 億美元。我們預計今年年底及以後新患者的數量將會增加。當然，一切都始於正確的藥物 AYVAKIT，這是一種具有廣泛標籤的有效療法，可以解決疾病的根本原因，並且耐受性非常好，使患者能夠開始並長期堅持治療。

Becker will discuss the growing body of evidence supporting AYVAKIT's long-term benefit in SM. In addition to AYVAKIT's compelling clinical profile, we know that what drives prescribing in this market is the powerful combination of an aware and ever-expanding educated prescriber base and an activated patient base, both recognizing the benefit and urgency to treat the root cause of disease with AYVAKIT now.

貝克爾將討論越來越多的證據支持 AYVAKIT 對 SM 的長期益處。除了 AYVAKIT 引人注目的臨床特徵之外，我們知道，推動這個市場處方的是一個有意識且不斷擴大的受過教育的處方者群體和活躍的患者群體的強大組合，他們都認識到現在使用 AYVAKIT 治療疾病根本原因的益處和緊迫性。

Let's start with prescribers. Since launch, we've been focused on increasing the breadth of our prescriber base through education and awareness. Driving awareness among allergy has been a key focus and is critical to long-term growth, as the providers managing the highest volume of SM patients are predominantly allergists.

讓我們從開處方者開始。自成立以來，我們一直致力於透過教育和宣傳來擴大我們的處方者基礎。提高人們對過敏症的認識一直是一個重點，對於長期成長至關重要，因為管理最多 SM 患者的提供者主要是過敏專家。

A first experience with AYVAKIT predictably leads to broader use in more patients. So a growing foundation of experienced prescribers directly drives growth in the number of patients starting AYVAKIT over time, increasing market penetration. Since ISM approval, our prescriber base in the US has tripled with adoption split across academic and community site care.

AYVAKIT 的首次使用體驗可望在更多患者中得到更廣泛的應用。因此，經驗豐富的處方人員隊伍的不斷壯大直接推動了開始使用 AYVAKIT 的患者數量的增長，從而提高了市場滲透率。自 ISM 批准以來，我們在美國處方藥數量增加了兩倍，採用情況在學術和社區站點護理中均有分佈。

Against the backdrop of a growing number of diagnosed patients, this creates an engine to drive growth in the number of patients prescribed AYVAKIT. What really catalyzes deepening of use over time are positive perceptions and experiences with AYVAKIT. Since ISM launched, we have conducted market research with over 700 providers.

在確診患者數量不斷增加的背景下，這為使用 AYVAKIT 的患者數量增長創造了動力。真正促進長期深化使用的是對 AYVAKIT 的正面看法和體驗。自 ISM 推出以來，我們已經對 700 多家供應商進行了市場調查。

Initial favorable perceptions of AYVAKIT from the PIONEER study results have grown even more positive with first-hand clinical experience and now with longer term data. Across all specialties, even dermatology and gastroenterology where we haven't yet started to deploy promotional effort, the vast majority of providers view AYVAKIT's profile as favorable.

PIONEER 研究結果對 AYVAKIT 的最初良好印象隨著第一手臨床經驗和現在的長期數據的累積而變得更加積極。在所有專業領域，甚至在我們尚未開始部署推廣工作的皮膚病學和胃腸病學領域，絕大多數提供者都對 AYVAKIT 的形象持讚賞態度。

Since launch, we've been targeting [hemocs] and allergists. Hemost treat less than a third of all ISM patients. We've talked about the importance of allergy for the long-term opportunity, and by expanding our call point to include derms and GIs, we will meaningfully increase the addressable patient pool.

自推出以來，我們的目標客戶一直是血液疾病患者和過敏症專家。Hemost 治療的 ISM 患者不到三分之一。我們已經討論了過敏對於長期機會的重要性，透過擴大我們的呼叫點以包括皮膚科和胃腸道科，我們將顯著增加可尋址的患者群。

Across these specialties, roughly 70% of the providers managing the highest volume of SM patients are allergists, derms, and GIs. This is why we're investing in expanding our field team to increase our reach and frequency where it matters most. Our field force expansion is designed to capitalize on where the majority of SM patients are treated.

在這些專業中，管理最多數量 SM 患者的提供者中約有 70% 是過敏症專家、皮膚科醫生和胃腸科醫生。這就是為什麼我們要投資擴大我們的現場團隊，以增加我們在最重要的領域的覆蓋範圍和頻率。我們的現場隊伍擴張旨在充分利用大多數 SM 患者接受治療的地方。

We've just hired new team members who are onboarding and training. They bring a diverse set of experiences with an emphasis on allergy, dermatology and rare disease. They'll be in the field by the second half of this year, and I look forward to the growth they'll catalyze in 2026 and beyond.

我們剛聘請了新團隊成員，正在進行入職培訓。他們擁有豐富的經驗，尤其註重過敏、皮膚科和罕見疾病。他們將於今年下半年投入使用，我期待他們在 2026 年及以後推動的成長。

AYVAKIT's positive reception among providers is matched by growing enthusiasm in the patient community. SM patients are highly engaged and active in their care decisions, and we're starting to see the clear impact of marketing efforts launched last year, including new direct-to-consumer and peer-to-peer programs.

AYVAKIT 在醫療服務提供者中獲得了積極的反響，而患者群體的熱情也日益高漲。SM 患者高度參與並積極參與他們的照護決策，我們開始看到去年推出的行銷活動的明顯影響，包括新的直接面向消費者和點對點計畫。

Providers report that significantly more of their ISM patients are asking about AYVAKIT compared to last year. And once patients are on treatment, they have a very positive experience, with over 95% of patients saying they're highly satisfied with AYVAKIT as a treatment for their SM.

提供者報告稱，與去年相比，詢問 AYVAKIT 的 ISM 患者明顯增多。一旦患者接受治療，他們就會獲得非常積極的體驗，超過 95％ 的患者表示他們對 AYVAKIT 治療 SM 非常滿意。

The SM market is highly promotionally sensitive, with the top two drivers being the efforts of our experienced sales team who are outperforming industry comps in promotional effectiveness scores and are direct to patient marketing efforts.

SM 市場對促銷高度敏感，其中最重要的兩個驅動力是我們經驗豐富的銷售團隊的努力，他們在促銷效果得分方面優於行業同行，並且直接針對患者的營銷努力。

Our growing base of experienced prescribers, an increasingly engaged and activated patient base and the compelling profile of AYVAKIT put us in a great place to drive growth in 2025. But we're not just focused on this year. We are on the path to driving continued growth towards $2 billion in revenue by 2030 and are committed to continue to grow this market well into the next decade.

我們經驗豐富的處方人員隊伍不斷壯大，患者群體的參與度和積極性不斷提高，加上 AYVAKIT 的卓越形象，使我們在 2025 年擁有良好的發展前景。但我們不僅僅關註今年。我們正朝著 2030 年實現 20 億美元收入的目標持續成長，並致力於在未來十年繼續推動這個市場的發展。

We plan to drive that growth by taking the same powerful combination of aware and educated prescribers with activated patients and amplifying it with a strategic investment in our field. We are confident in our multi-faceted approach to develop and capture this market.

我們計劃透過有意識和受過教育的處方者與積極患者之間的強大組合來推動這一成長，並透過對我們領域的策略性投資來擴大這一成長。我們對採用多管齊下的方法來開發和佔領這個市場充滿信心。

I'll now hand the call over to Becker to share clinical updates across our portfolio.

我現在將電話交給貝克爾，讓他分享我們整個產品組合的臨床更新。

Thanks, Philina. First, I want to talk about AYVAKIT's long-term data in systemic mastocytosis that we presented at quad AI and that Philina just referenced. What was remarkable in PIONEER is that the safety profile of AYVAKIT was superior to best supportive care at six months, a rare occurrence for an efficacious treatment.

謝謝，菲莉娜。首先，我想談談我們在 quad AI 上展示的以及 Philina 剛才提到的 AYVAKIT 在系統性肥大細胞增多症方面的長期數據。PIONEER 的顯著特點是，AYVAKIT 的安全性在六個月時優於最佳支持性治療，這對於有效治療而言是罕見的。

Now, after three full years of treatment, we see the same safety profile. This is extraordinary in my experience. Generally, the safety profile becomes more complex over time. But for AYVAKIT, the frequency and severity of treatment-related adverse events have been consistent and remain low throughout three years.

現在，經過整整三年的治療，我們看到了相同的安全性。在我的經歷中，這是非同尋常的。一般來說，安全性概況會隨著時間的推移而變得更加複雜。但對於AYVAKIT而言，治療相關不良事件的頻率和嚴重程度在三年內保持一致且維持在較低水準。

And importantly, only 3% of patients discontinued due to treatment-related adverse events over this extended time frame. The 25 milligram dose of AYVAKIT provides an exceptional benefit risk profile for the vast majority of patients. In our real-world post-marketing experience, more than 90% of patients who start at 25 milligram stay at that dose.

重要的是，在這段延長的時間內，只有 3% 的患者因治療相關的不良事件而停藥。25 毫克劑量的 AYVAKIT 為絕大多數患者提供了卓越的效益風險狀況。在我們實際的上市後經驗中，超過 90% 以 25 毫克開始服用的患者會維持該劑量。

The patients are highly compliant, satisfied and our discontinuation rates are very low. However, we know that there is a spectrum of disease severity in systemic mastocytosis, and a one dose fits all approach is not appropriate in this disease. The PIONEER study included patients with very high disease. We've enabled more severe patients to do escalate to 50 milligram in Part 3 of the study.

患者的依從性很高，滿意度也很高，而且我們的停藥率非常低。然而，我們知道系統性肥大細胞增多症的嚴重程度各不相同，對於這種疾病，採用一劑適合所有人的治療方法並不合適。PIONEER 研究納入了病情非常嚴重的患者。在研究的第 3 部分中，我們已讓病情更嚴重的患者將劑量增加到 50 毫克。

We recently presented data showing that these patients have had a safety profile consistent with that we've seen at 25 milligram. Efficacy continues to improve for PIONEER patients, as indicated by durable responses measured by TSF and quality of life measurements through three years.

我們最近提供的數據顯示這些患者的安全性與我們在 25 毫克劑量下觀察到的數據一致。TSF 測量的持久反應和三年來的生活品質測量表明，PIONEER 患者的療效持續提高。

Among the patient subsets and PIONEER who titrated their dose to 50 milligram, 93% of patients saw improved or stable TSF benefit at 50 milligram without any trade-off and safety. We're expanding our commercial and medical reach to an even larger target physician audience of allergists, dermatologists and gastroenterologists with multiple years of consistent data demonstrating that AYVAKIT is a safe and effective treatment in.

在將劑量滴定至 50 毫克的患者亞群和 PIONEER 中，93% 的患者在 50 毫克時獲得改善或穩定的 TSF 益處，且沒有任何權衡和安全性。我們正在將商業和醫療範圍擴大到更大的目標醫生群體，包括過敏症專家、皮膚科醫生和胃腸病學家，多年來的一致數據證明 AYVAKIT 是一種安全有效的治療方法。

This helps drive comfort in trying a new therapy and prescribing AYVAKIT. Finally, we continue to advance the science of systemic mastocytosis in the HARBOR study of elenestinib. Our study design explores disease modifying measures of clinical benefit, notably the impact on bone health and recurrent anaphylaxis. These have been enthusiastically received by investigators, and they report also from patients interested in the study.

這有助於讓人們安心嘗試新療法並開出 AYVAKIT。最後，我們繼續在 elenestinib 的 HARBOR 研究中推進系統性肥大細胞增多症的科學研究。我們的研究設計探討了具有臨床益處的疾病改良措施，特別是對骨骼健康和復發性過敏反應的影響。這些研究受到了研究人員的熱烈歡迎，他們也報告了對該研究感興趣的患者的情況。

Turning now to our wild type kit inhibitor BLU-808. At quad AI this year, we presented data from the healthy volunteer study, and with this promising data in hand, we're moving into four proof-of-concept studies this year. We know that a strong safety profile is critical in the field of allergic disease. And with BLU-808, we have a wide therapeutic index to work within.

現在轉向我們的野生型試劑盒抑制劑 BLU-808。在今年的四重人工智慧大會上，我們展示了健康志願者研究的數據，有了這些有希望的數據，我們今年將進行四項概念驗證研究。我們知道，在過敏性疾病領域，強大的安全性至關重要。有了 BLU-808，我們就有更廣泛的治療指數可供運用。

We're building in a range of flexible dose strategies across these studies, including consistent dosing, induce and maintain and titrate to effect, which we know is in line with how allergists treat. We've initiated our first two proof-of-concept studies, one in allergic rhinoconjunctivitis and one in chronic urticaria.

我們在這些研究中建立了一系列靈活的劑量策略，包括一致劑量、誘導和維持以及滴定至效果，我們知道這與過敏症專家的治療方式一致。我們已經啟動了前兩項概念驗證研究，一項針對過敏性鼻結膜炎，另一項針對慢性蕁麻疹。

We will be initially testing doses between 1 and 6 milligram. This covers the IC-90 well and will allow us to examine a spectrum of biologic impact that ranges from calming or stopping mass cells from degranulating to killing them entirely. This will allow us to determine the impact on symptoms so that we can achieve the right balance of safety and efficacy for chronic treatment.

我們最初將測試 1 至 6 毫克之間的劑量。這很好地涵蓋了 IC-90，並使我們能夠檢查一系列生物學影響，從鎮靜或阻止大量細胞脫顆粒到徹底殺死它們。這將使我們能夠確定對症狀的影響，以便我們能夠實現慢性治療的安全性和有效性的適當平衡。

I'll start with chronic urticaria, where the role of mast cells as the key driver of disease is already well established. In our proof-of-concept study, we're using this indication to explore various dosing regimens for BLU-808.

我先從慢性蕁麻疹開始，肥大細胞作為此病的主要驅動因素的作用已得到充分證實。在我們的概念驗證研究中，我們正在利用此適應症來探索 BLU-808 的各種給藥方案。

Our initial 12-week Phase 2A study will include two key parts, an open label study of patients with chronic inducible urticaria and a randomized double-blind placebo-controlled study of patients with chronic spontaneous urticaria. Both parts will include multiple doses and dosing regimens.

我們最初的 12 週 2A 期研究將包括兩個關鍵部分，一項針對慢性誘發性蕁麻疹患者的開放標籤研究和一項針對慢性自發性蕁麻疹患者的隨機雙盲安慰劑對照研究。這兩個部分都將包括多種劑量和給藥方案。

Our goal is for BLU-808 to become an attractive oral option that achieves that balance of tolerability and efficacy and differentiates us from the rest of the field. Now, let me turn to the phase 2A study in allergic rhinoconjunctivitis.

我們的目標是讓 BLU-808 成為一種有吸引力的口服藥物，實現耐受性和療效的平衡，並使我們在該領域中脫穎而出。現在，讓我來談談過敏性鼻結膜炎的 2A 期研究。

We see this as a way to demonstrate the activity of BLU-808 in the respiratory tract. This is a 28 day placebo-controlled challenge study where patients are exposed to allergen, then treated with BLU-808 or placebo, and then re-exposed to compare their before and after treatment reaction.

我們認為這是展示 BLU-808 在呼吸道中的活性的一種方式。這是一項為期 28 天的安慰劑對照激發研究，患者接觸過敏原，然後用 BLU-808 或安慰劑治療，然後再次接觸以比較治療前後的反應。

Similar to chronic urticaria, in this study, we will assess multiple doses for safety, PK and clinical efficacy. We expect to have some early data by the end of this year in the [sindu] cohort. In the second half of the year, we planned to initiate studies in allergic asthma and in MCAS.

與慢性蕁麻疹類似，在本研究中，我們將評估多種劑量的安全性、PK 和臨床療效。我們預計今年年底前將獲得 [sindu] 隊列的一些早期數據。下半年，我們計劃啟動過敏性氣喘和MCAS的研究。

We discussed the role of the mast cells in allergic asthma at our webinar last year, and similarly planned to share Blueprint's approach to MCAS at our webinar on June 4 with Dr. Matt Giantti, the leading expert in mast cell diseases at the Brigham and Women's Hospital here in Boston. Results from these proof of concept studies will help guide BLU-808 development plans as we work towards improving the lives of patients with mast cell-driven diseases.

我們在去年的網路研討會上討論了肥大細胞在過敏性氣喘中的作用，並計劃在 6 月 4 日的網路研討會上與波士頓布萊根婦女醫院肥大細胞疾病領域的頂尖專家 Matt Giantti 博士分享 Blueprint 對 MCAS 的處理方法。這些概念驗證研究的結果將有助於指導 BLU-808 開發計劃，我們致力於改善肥大細胞驅動疾病患者的生活。

Now, I'll turn the call over to Mike.

現在，我將把電話轉給麥克。

Thanks, Becker. Earlier this morning, we reported detailed financial results in our press release, and for today's call I'll touch on a few highlights. In the first quarter, we achieved total revenues of $149.4 million from net product sales of AYVAKIT.

謝謝，貝克爾。今天早些時候，我們在新聞稿中報告了詳細的財務結果，在今天的電話會議上，我將談到一些亮點。第一季度，AYVAKIT 的淨產品銷售額總收入為 1.494 億美元。

Based on the positive fundamentals that Philina discussed, as well as the additional insight we gained around free goods in Q1, we are raising our AYVAKIT net product revenue guidance to $700 million to $720 million for the year.

根據 Philina 討論的正面基本面，以及我們在第一季度獲得的有關免費商品的額外見解，我們將 AYVAKIT 淨產品收入預期上調至今年 7 億至 7.2 億美元。

Consistently strong fundamentals and continued growth in new patient starts in all markets will continue to drive performance through the remainder of the year. For our international business, the timing and outcome of ongoing pricing and reimbursement negotiations are another consideration.

持續強勁的基本面和所有市場新患者數量的持續成長將繼續推動今年剩餘時間的業績。對於我們的國際業務，正在進行的定價和報銷談判的時間和結果是另一個考慮因素。

Turning to operating expenses, we observed an incremental quarter over quarter increase in R&D expenses related to elenestinib and BLU-808 clinical studies. SG&A expenses were flat in the first quarter relative to the prior quarter, and we anticipate that we will see continued modest increases in both R&D and SG&A expenses as we invest in our priority pipeline programs, as well as increase investment in our sales and marketing efforts for AYVAKIT, as Philina spoke to in detail earlier on the call.

談到營運費用，我們觀察到與 elenestinib 和 BLU-808 臨床研究相關的研發費用逐季增加。第一季的銷售、一般及行政費用與上一季持平，我們預計，隨著我們對優先管道項目的投資，以及對 AYVAKIT 銷售和營銷工作的投資增加，研發和銷售、一般及行政費用將繼續小幅增長，正如 Philina 在早些時候的電話會議上詳細談到的那樣。

We continue to expect that our operating cash burn will decline significantly on an annual basis. To reinforce what Kate said earlier in the call, we are in an incredible position of strength today, particularly when you consider the macroeconomic environment. We have strong and consistent topline revenue growth driven by global sales of AYVAKIT.

我們仍然預計我們的營運現金消耗將逐年大幅下降。為了強調凱特早些時候在電話會議上所說的話，我們今天處於一個令人難以置信的強大地位，特別是當你考慮到宏觀經濟環境時。在 AYVAKIT 全球銷售的推動下，我們的營業收入實現了強勁且持續的成長。

The ability to continue to invest in innovation to drive future growth and a strong and durable cash position of $900 million. Our commercial and financial profile stands out among biotech as a positive differentiator, and now more than ever before, we are in a position of incredible strength to drive sustained growth for the long term.

有能力繼續投資創新以推動未來成長，並擁有 9 億美元的強勁持久現金狀況。我們的商業和財務狀況在生物技術領域脫穎而出，成為積極的差異化因素，現在我們比以往任何時候都更有能力推動長期持續成長。

With that, I'll turn the call back over to the operator for questions. Operator?

說完這些，我將把電話轉回給接線生以回答問題。操作員？

(Operator Instructions) Marc Frahm, TD Cowen.

（操作員指示）Marc Frahm，TD Cowen。

Hey. Thanks for taking my questions. First, on the commercial side, can you frame the type of rebound growth or acceleration of growth you might see in Q2, given the fact that the free goods is already so low, which maybe limit some of the typical Q1 to Q2 rebounds that we see that we see across the industry.

嘿。感謝您回答我的問題。首先，從商業方面來看，考慮到免費商品的數量已經很低，您能否預測一下第二季度可能出現的反彈增長或加速增長類型，這可能會限制我們在整個行業中看到的一些典型的第一季到第二季度的反彈。

And then on the R&D side, for the 808, just talk to the strategy on the dose selections that you put into those. Are the two doses supposed to really test that intermediate range with the titration, or are you trying to maybe with the top dose really show the full power of 808 and inability to get close to it not matching the antibodies?

然後在研發方面，對於 808，只需討論您在其中採用的劑量選擇策略。這兩種劑量是否真的應該透過滴定來測試中間範圍，或者您是否試圖透過最高劑量真正顯示 808 的全部功效並且無法接近與抗體不匹配的功效？

Yeah. Thanks, Marc, for that question. Maybe Christy, if you want to talk a little bit about how we've considered the fundamental growth and the drivers of demand and as we think through the year and then maybe to please add color, Becker, you can add into the question.

是的。謝謝馬克提出這個問題。也許克里斯蒂，如果你想稍微談談我們如何考慮基本成長和需求驅動因素，以及我們如何思考這一年，然後也許請添加一些色彩，貝克爾，你可以添加到問題中。

Sure. Hey, Marc. So if we think about the year, we obviously updated guidance. And so, if I think about the remaining three quarters, I would certainly think about the guide and that guide does imply growth, which is really what we expected when we set guidance at the beginning of the year as well.

當然。嘿，馬克。因此，如果我們考慮今年的情況，我們顯然會更新指導。因此，如果我考慮剩下的三個季度，我肯定會考慮指南，而指南確實意味著成長，這也是我們在年初設定指南時所預期的。

We always knew that Q1 was going to be challenging for all of the reasons that Philina said, but what we expected to see was strong underlying growth in terms of those drivers of the longer-term potential for AYVAKIT, which includes patients starting, persistence duration, et cetera.

我們一直都知道，由於 Philina 所說的所有原因，第一季將會充滿挑戰，但我們預計看到的是，AYVAKIT 長期潛力的驅動因素將實現強勁的潛在成長，包括患者開始用藥、持續時間等。

And so, that's exactly what we've see and that's played out in line with our expectations. And so, if you play that forward through the year, we would expect to see growth in the remaining quarters. The one wrinkle we saw in Q1 around a shorter quarter from an ordering perspective, I believe, if I'm not mistaken, it's made up actually in Q3, interestingly enough, but we definitely expect to see nice steady growth as we go through the remainder of the year.

這正是我們所看到的，並且符合我們的期望。因此，如果按照這一思路推算全年，我們預計剩餘幾季將會出現成長。從訂購角度來看，我們在第一季看到的一個問題是季度較短，如果我沒記錯的話，我相信，有趣的是，它實際上在第三季度得到了彌補，但我們肯定預計，在今年剩餘時間內，我們將看到良好的穩定增長。

Let's say, in our results this year, really our big card flip in Q1 was around how we're going to see free goods play through. And I don't know, Philina, do you want to talk a little bit more about that.

可以說，在今年的業績中，我們第一季的重大轉折點實際上是圍繞著如何看待免費商品的表現。我不知道，菲莉娜，你是否想再多談一點這個話題。

Yeah. As we entered the year, I think one of the biggest variables that we had that informed our guidance range was that we had a large book of business, i.e., a really large number of patients, and we didn't know to what extent these patients would be able to transition and access paid versus free goods.

是的。進入新的一年，我認為影響我們指導範圍的最大變數之一是我們有大量的業務，即大量的患者，我們不知道這些患者在多大程度上能夠轉變並獲得付費或免費商品。

Over the course of Q1, like this is a big variable that has been tremendously de-risked and that has been one of the key drivers for our guidance update together with the expected growth in the underlying fundamentals, i.e., growth in patients on therapy as Christy just said.

在第一季度，像這樣的一個大變數已經大大降低了風險，並且是我們更新指導意見的關鍵驅動因素之一，同時還有基本面的預期增長，即克里斯蒂剛才所說的接受治療的患者數量的增長。

So I think at this point thinking about the free goods trends, looking for the rest of the year, certainly, the range has narrowed. We have a better sense of the range to expect. We're below 10%. We don't expect this to really be able to go appreciably down further.

因此，我認為，從目前的情況來看，考慮免費商品的趨勢，展望今年剩餘時間，範圍肯定已經縮小。我們對預期範圍有了更好的了解。我們低於10%。我們並不認為這一數字能夠進一步大幅下降。

And really over the rest of the year, we'll need to be watching as new Medicare patients come on therapy, their ability to access commercial versus free drug, but I would just take it back to the trajectory that we're seeing in Q1 we firmly believe puts us on pace for our guidance as well as marching towards that $2 billion by 2030.

實際上，在今年剩餘的時間裡，我們需要專注於新的醫療保險患者接受治療的情況，以及他們獲得商業藥物和免費藥物的能力，但我只想回顧一下我們在第一季看到的軌跡，我們堅信這將使我們步入指導步伐，並朝著 2030 年實現 20 億美元的目標邁進。

Becker, do you want to talk about the second question?

貝克爾，你想談第二個問題嗎？

Sure. Let me talk about the dose range of BLU-808 and how we selected this and what our strategy is here. Just a reminder that we do have all three regimens, one which is consistent dosing, the other which is an induce and maintain, which will look at speed to symptom resolution and then our ability with a lower dose to maintain that symptom resolution.

當然。讓我來談談 BLU-808 的劑量範圍以及我們如何選擇它以及我們的策略是什麼。需要提醒的是，我們確實有三種方案，一種是持續劑量，另一種是誘導和維持，這將著眼於症狀消退的速度，然後以較低的劑量維持症狀消退的能力。

And then one where will allow titration to the effect. And I think it's important to remember that in many diseases, including chronic urticaria, there are a multitude of symptoms. And really driving the relief of the patient at the right dose is what we're exploring, and we're doing it in a way that the antibodies really can't do.

然後，就可以進行滴定以達到效果。我認為重要的是要記住，許多疾病，包括慢性蕁麻疹，都有多種症狀。我們正在探索以正確的劑量真正緩解患者的病情，而且我們正在以抗體無法做到的方式做到這一點。

So we're going to better understand the biology of the disease and the response with respect to the symptomatology as we use these different dosing strategies. And the intent of the study is to really set things up for the next phase of studies in chronic urticaria and in other indications where we get the optimized dosing for each of these indications.

因此，當我們使用這些不同的給藥策略時，我們將更了解疾病的生物學特性以及對症狀的反應。研究的目的是為慢性蕁麻疹和其他適應症的下一階段研究做好準備，我們將針對每種適應症獲得最佳劑量。

As we said earlier, the 1 to 6 milligrams gives us a range that covers the IC-90 well, and we all mass cells don't die at once. And so, we'll look at different levels of killing in different patients to better understand killing dose and a dose that's designed to calm down the mast cells.

正如我們之前所說，1 至 6 毫克為我們提供了一個可以很好地覆蓋 IC-90 的範圍，並且我們所有的細胞都不會同時死亡。因此，我們將研究不同患者的不同殺傷水平，以更好地了解殺傷劑量和旨在鎮靜肥大細胞的劑量。

With respect to comparisons, again, these studies are designed to help us understand how to use the drug, and then to understand the full efficacy in the next wave of studies, we will bring that optimized dosing into a more definitive study.

關於比較，這些研究旨在幫助我們了解如何使用該藥物，然後在下一波研究中了解其全部功效，我們將把優化劑量納入更明確的研究中。

Laura Prendergast, Raymond James.

勞拉·普倫德加斯特、雷蒙德·詹姆斯。

Hey, guys. Congrats on the progress of this quarter. Just may be to reiterate that question, what exactly have you guys baked into the guidance, any expected seasonality, EU contribution, any specific tailwinds or headwinds on new starts that you expect?

嘿，大家好。恭喜本季取得的進展。可能只是想重申這個問題，你們究竟在指導中考慮了什麼，任何預期的季節性、歐盟的貢獻，以及您預期的新開工的任何具體順風或逆風？

And then, just if you guys could comment on Part 2 HARBOR data, when should we expect that and is any elenestinib data priced into the $2 billion by 2030 -- the $2 billion by 2030, is that pricing in elenestinib and being on the market? Thank you.

然後，如果你們可以對第 2 部分 HARBOR 數據發表評論，我們應該何時預期，以及任何 elenestinib 數據是否計入 2030 年的 20 億美元 - 2030 年的 20 億美元，是否計入了 elenestinib 的價格並上市？謝謝。

Thanks, Laura. Just a reminder, everybody, let's try to keep it to one question just given the number of people we have in the queue, but we'll try to handle some other things offline if we can. Maybe Christy, will you take the guidance question and then Becker, we can talk about Part 2 HARBOR.

謝謝，勞拉。提醒一下各位，考慮到排隊人數，我們盡量只問一個問題，但如果可以的話，我們會嘗試離線處理一些其他事情。也許克里斯蒂，你願意回答指導問題，然後貝克爾，我們可以討論第二部分 HARBOR。

I can just clarify right away there's nothing from an elenestinib perspective in the $2 billion by 2030, that's completely driven by AYVAKIT, and we expect AYVAKIT to grow beyond that to be honest. So just so I can take that one. Christy, do you want to talk about guidance?

我可以立即澄清的是，從 elenestinib 的角度來看，到 2030 年的 20 億美元並不完全是由 AYVAKIT 推動的，而且說實話，我們預計 AYVAKIT 的成長速度會超越這一水平。這樣我就可以接受這個了。克里斯蒂，你想談談指導嗎？

Sure. So the factors that we think about with guidance are very much consistent with how we framed it at the beginning of the year. Actually, we talked about it last year, right? So the two biggest determinants in my mind of AYVAKIT getting to $2 billion by 2030 and the $4 billion opportunity we see across the SM franchise over time is really treating more patients, right?

當然。因此，我們在指導中考慮的因素與我們年初制定的指導思想非常一致。其實我們去年就討論過這個了，對吧？因此，在我看來，AYVAKIT 到 2030 年實現 20 億美元銷售額以及 SM 特許經營權隨著時間的推移實現 40 億美元銷售額的機會這兩個最大的決定因素實際上是治療更多的患者，對嗎？

So having patients start on therapy and having them continue to stay on therapy. So those are the two big drivers, and we expect to see growth in new patients starts as they go through the year based on our expanding breadth and depth of prescribing that we're seeing in the US, and increasingly activated patient base, et cetera.

因此，讓患者開始接受治療並讓他們繼續接受治療。因此，這是兩個主要驅動因素，我們預計，隨著我們在美國看到的處方廣度和深度的不斷擴大，以及患者群的日益活躍等，新患者的數量將在今年內增長。

This is obviously still in the context of our disease market. You're going to see fluctuations there, but the overall trend line is clear and positive. We expect to see strength and duration of therapy as patients are staying on therapy for, we think, three years-plus potentially multiple years here.

這顯然還是在我們的疾病市場的背景下。你會看到那裡有波動，但總體趨勢線是清晰和積極的。我們期望看到治療的強度和持續時間，因為我們認為患者將接受治療三年以上，甚至可能數年。

And so, those are two of the most important variables as we go over time. Then there's a number of other things that actually may have more impact in the short term. And so, we think about gross to net, free goods rates, et cetera. And then of course our international business is coming along.

因此，隨著時間的推移，這是兩個最重要的變數。此外，還有許多其他因素實際上可能會在短期內產生更大的影響。因此，我們考慮總額與淨額、免稅商品率等等。當然，我們的國際業務也在不斷發展。

So those are (technical difficulty) Philina said, we had a major, I would say, card slip in the first quarter by understanding how a very large base of patients who are now on therapy as they went through the re-verification process, understanding how that free commercial mix was going to play out.

所以這些都是（技術難題）菲利娜說，我想說，我們在第一季度遇到了一個重大的卡片失誤，透過了解現在正在接受治療的大量患者在重新驗證過程中的情況，了解免費商業組合將如何發揮作用。

We knew it was going to be important, we knew that was going to be a big swing as we thought about top line revenue. And so, we're really pleased to see how that played out in the first quarter and also pleased to see continued strength along the other variables that we've mentioned that really again portend that longer term potential.

我們知道這很重要，我們知道當我們考慮營業收入時這將是一個巨大的轉變。因此，我們很高興看到第一季的進展，也很高興看到我們提到的其他變數繼續保持強勁，這再次預示著長期潛力。

So those are still going to be the things that we'll continue to watch. There's ranges of outcomes on all of those variables but pleased to see that we were able to raise the guidance of Q1 performance and in terms of quarter-to-quarter performance.

因此，這些仍將是我們會持續關注的事情。所有這些變數的結果都有一系列的變化，但很高興看到我們能夠提高第一季業績和季度環比業績的預期。

We know our business. You talked about things like seasonality, et cetera. We've now far enough into this launch where I think we have a good sense of how these factors will play out in terms of impacting quarter to quarter revenue. We've baked that into the guide. And in fact, it baked it in when we started the year and expected Q1 to play out as it did.

我們了解我們的業務。您談到了季節性等等的事情。現在我們已經對這次發布有了足夠的了解，我認為我們已經很清楚這些因素將如何影響季度收入。我們已將其納入指南中。事實上，當我們年初時，我們就考慮到了這一點，並預計第一季會出現這樣的情況。

Becker, do you want to talk a little bit about HARBOR -- obviously, we're just getting this up and running now.

貝克爾，你想談談 HARBOR 嗎？顯然，我們現在才剛開始啟動它。

So we're just starting this study. We have a highly motivated group of investigators and I'm hearing patients as well who are very interested in the study. As we see the evolution of the systemic mastocytosis in the world and we see how this study unfolds, we'll be able to keep you all more well informed about when we might see topline data, but I think it's premature to speculate at this point.

所以我們才剛開始這項研究。我們擁有一支積極性很高的研究人員團隊，而且我聽說患者也對這項研究非常感興趣。隨著我們看到系統性肥大細胞增多症在世界範圍內的發展以及這項研究的進展，我們將能夠讓大家更清楚地了解何時可以看到頂線數據，但我認為現在進行推測還為時過早。

Michael Schmidt, Guggenheim.

古根漢美術館的麥可·施密特。

Hey, this is Paul for Michael. Thanks for taking our question. Just on AYVAKIT, so for the ex-US, it looks like it was flat quarter on quarter. Can you just comment on what your overall expectations are for the international market drivers this year, including when ISM reimbursement beyond Germany could start to kick in.

嘿，我是保羅，代表麥可。感謝您回答我們的問題。僅就 AYVAKIT 而言，對於美國以外的地區而言，看起來季度環比持平。您能否評論一下您對今年國際市場驅動因素的整體預期，包括德國以外的 ISM 補償何時開始生效。

And then maybe a quick follow up on those escalations that you mentioned in ISM patients. Your quad AI data suggested around a quarter escalated to 50 milligrams. What's your current visibility into what percentage of commercial patients have booked 50 for ISM? Thank you.

然後也許可以快速跟進一下您在 ISM 患者中提到的那些升級情況。您的四重 AI 數據顯示大約四分之一升級到 50 毫克。您目前了解有多少比例的商業患者已為 ISM 預約了 50 名患者？謝謝。

Yeah. Thanks for the question. And we'll start, Christy, you take international and then Philina, you talk a little bit about what we're seeing in dosing. One thing I should say is the international teams have just done a tremendous job and their year over year performance more than doubled from Q1 last year. So we're really excited about where we are. But you want to talk about the Q4 to Q1 dynamic, Christy?

是的。謝謝你的提問。首先，克里斯蒂，你談談國際問題，然後菲利娜，你談談我們在劑量方面看到的情況。我要說的是，國際團隊剛剛完成了一項了不起的工作，他們的同比業績比去年第一季增長了一倍多。所以我們對於現在的狀況感到非常興奮。但是你想談談 Q4 到 Q1 的動態嗎，克里斯蒂？

Yeah. Absolutely. So right, as Kate said, the international team has been doing very well. We've talked about the fact that, if we think about this contributions to the topline, last year, we expected it to be in that 10% to 15% range.

是的。絕對地。正如凱特所說，國際團隊表現非常出色。我們已經討論過這樣一個事實，如果我們考慮這對去年營業額的貢獻，我們預計它將在 10% 到 15% 的範圍內。

This year, on a much bigger base we expect it to also be within the 10% to 15% range, right? So the international team continues to perform and we're seeing nice growth there. It's important to remember that Germany is the only ex-US market with ISM reimbursement at this point.

今年，在更大的基數上，我們預計它也將在 10% 到 15% 的範圍內，對嗎？因此，國際團隊繼續表現出色，我們看到了良好的成長。重要的是要記住，德國是目前唯一一個獲得 ISM 補償的美國以外市場。

We do expect some others to come online through the year, but we'll really start to see ISM growth across a number of markets as we head even into next year and beyond. The business in Germany is doing quite well. We're continuing to see trends that look very similar to the US, which has been really encouraging to see.

我們確實預計今年還會有一些其他產品上線，但隨著進入明年及以後，我們將真正開始看到多個市場的 ISM 成長。德國的業務開展得相當不錯。我們繼續看到與美國非常相似的趨勢，這確實令人鼓舞。

So nice growth and patients being treated, very similar trends in terms of uptake. Fluctuations can happen quarter to quarter. There were some things between Q4 and Q1, for example, like timing of distributor orders which can be lumpy, a little bit of FX at the beginning of the year.

增長情況和接受治療的患者情況都呈現出非常相似的趨勢。每個季度都可能出現波動。例如，第四季和第一季之間出現了一些情況，例如經銷商訂單的時間安排可能不太穩定，年初出現了一些外匯波動。

We're still talking about a relatively small revenue base relative to the US, right? So these little factors can obviously have a role when we look at Q1 and we've seen that before if you go back and look at international performance over the last year or so. But the bigger picture is that business is doing well, German launch is doing really well, and we're looking ahead and looking forward to having some other ISM launches come online.

我們仍在談論相對於美國而言相對較小的收入基礎，對嗎？因此，當我們看第一季時，這些小因素顯然會發揮作用，如果你回顧過去一年左右的國際表現，我們會發現這一點。但總體而言，業務進展順利，德國的發表會進展順利，我們展望未來，並期待其他 ISM 產品的推出。

And so, the question on dosing, the 25 mg benefit risk profile continues to serve the vast majority of patients very well. It's under 10% of patients that we're seeing who may dose escalate to 50 mgs over time, and this is occurring against the backdrop of the profile of the 25 mg holding strong and improving with continued long term efficacy and safety outcomes. We also see this reflected in just the really positive sentiment for AYVAKIT reflected in both our provider and patient satisfaction.

因此，關於劑量的問題，25 毫克的益處風險概況仍然能夠很好地服務於絕大多數患者。我們看到，不到 10% 的患者可能會隨著時間的推移將劑量增加到 50 毫克，而這種情況發生的背景是，25 毫克的療效保持強勁，並且隨著長期療效和安全性結果的持續改善。我們也看到這一點反映在對 AYVAKIT 的正面情緒中，無論是我們的供應商還是患者的滿意度都反映了這一點。

And just one thing to add to that is that even what Becker showed you from both the safety and efficacy of the 50 mgs is that what we see is that with AYVAKIT, at 25 milligrams or 50 milligrams, patients don't have to weigh a trade-off between efficacy and safety.

還有一點要補充的是，即使貝克爾向您展示了 50 毫克的安全性和有效性，我們也看到，使用 25 毫克或 50 毫克的 AYVAKIT，患者不必在有效性和安全性之間權衡。

And they can experience a very low treatment burden that really allows them to just get back to their lives and with a medicine that really empowers them to live and do the things they want to do. So both the 25 and 50 have really come through in a very nice way for these patients.

而且他們的治療負擔很輕，可以讓他們真正地恢復正常生活，並且透過藥物讓他們能夠真正地生活和做他們想做的事情。因此，25 和 50 對這些患者來說確實起到了非常好的作用。

And the other thing to remember is that the PIONEER population was a highly advanced patient population, enrolled in the middle of a pandemic, first study out there with a really effective therapy. And so, it's probably not indicative of what will be seen in the real world.

另外要記住的是，PIONEER 族群是處於高度晚期的患者群體，他們在疫情期間入組，是第一個採用真正有效療法進行的研究。因此，它可能無法反映現實世界中會看到的情況。

Michael Yee, Jefferies.

麥可‧餘 (Michael Yee)，傑富瑞集團 (Jefferies)。

Thanks. Good morning. Congrats on the continued growth. I'm thinking about growth for the rest of the year. I know you've gotten a bunch of questions about headwinds and tailwinds and different dynamics. Can you help give some color as to perhaps the trajectory or shape of the curve in Q2, 3, 4?

謝謝。早安.恭喜您繼續成長。我正在考慮今年剩餘時間的成長。我知道你們已經收到了很多關於逆風、順風和不同動態的問題。您能否幫忙解釋 Q2、3、4 中的曲線軌跡或形狀？

Is it consistent year over year growth in each quarter? Are there different things that impacted those quarters and as part of that perhaps even OUS given that it appeared to be more flattish and just wondering if that's a factor as well into any of these quarters for the rest of the year. Thank you.

每季的年增率是否一致？是否有不同的因素影響了這些季度，甚至可能是 OUS 的一部分，因為它似乎更加平穩，我只是想知道這是否也是今年剩餘時間任何季度的一個因素。謝謝。

Thanks, Michael. So I think what you're asking is how to think about the remainder of the year. Obviously, we're really focused here on how we're exiting the year because that is what really drives us to that laser focus on that $2 billion by 2030 but understand that you guys want to get a sense of how we're thinking about the quarters. I don't know, Mike, if you want to provide a little bit color and how do you think about that.

謝謝，麥可。所以我認為你想問的是如何考慮今年剩餘的時間。顯然，我們真正關注的是我們如何結束這一年，因為這才是真正促使我們到 2030 年將重點放在實現 20 億美元目標上的原因，但請理解，你們想了解我們對各個季度的看法。我不知道，麥克，你是否願意提供一點色彩，以及你對此有何看法。

Yeah. I'll start. I mean, I think what's most important is to put this in the frame of what our updated overall annual guidance is and using that like that's the benchmark that we're guiding too. And as we've talked about before, like each quarter can have unique variables in the US and international.

是的。我先開始。我的意思是，我認為最重要的是將其置於我們更新的年度整體指導框架內，並將其作為我們指導的基準。正如我們之前討論過的，每個季度在美國和國際上都會有獨特的變數。

I think the one thing that Christy mentioned that we did want to point to if you think about like the growth especially over like Q2, Q3, it's like we've talked about we've missed an order day in Q1, right? That actually gets made up in Q3 in the calendar and just for context like our biggest customers tend to order on the same day each week.

我認為克里斯蒂提到的一件事是我們確實想指出的，如果你考慮成長，特別是第二季、第三季的成長，就像我們談到的，我們在第一季度錯過了一個訂單日，對吧？這實際上是在日曆的第三季度中完成的，只是為了了解我們最大的客戶傾向於每周同一天訂購的情況。

We had one less of those in Q1. It gets made up in Q3. So right there you're going to see a differential dynamic between Q2 and Q3, where you'd say there's probably a little bit more, shifted into the Q3 period, but fundamentally I just point to consistent underlying patient growth, and that's been as expected and we continue to drive towards that as we go for the updated guidance range.

我們在第一季就少了一個這樣的人。它將在第三季度得到彌補。因此，您會看到第二季度和第三季度之間的差異動態，您可能會說可能會有更多變化轉移到第三季度，但從根本上來說，我只是指出持續的潛在患者增長，這是預期的，我們會繼續朝著這個方向努力，以達到更新的指導範圍。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Great. Good morning. Thanks for taking our questions and congrats on all the progress. One quick one from us for the growth this year. Can you talk to how much of that is driven by the newer specialties that you're going after in terms and GIs versus the allergist and hemocs that your first target prescribers?

偉大的。早安.感謝您回答我們的問題，並祝賀我們取得的所有進展。我們簡單介紹一下今年的成長情況。您能否談談其中有多少是由您所追求的較新的專業領域所推動的，例如胃腸道疾病，以及您的首要目標處方醫生過敏症和血液病？

Yeah. Thanks, Colleen. Philina, do want to talk about how you're thinking about the prescriber mix this year versus next year, I guess.

是的。謝謝，科琳。菲莉娜，我想您確實想談談您對今年和明年的處方組合有何看法。

Yeah. Thanks for the question. So I think as Christy started alluding to we expect growth -- we expect to drive increased treatment rates and growth in the number of patients on therapy. We have a strong engine in place to do this already with what we've established across our target specialties and an increasingly activated patient base.

是的。謝謝你的提問。因此，我認為，正如克里斯蒂開始提到的，我們預計會出現成長——我們預計治療率會提高，接受治療的患者數量也會增加。我們已經擁有強大的引擎來實現這一目標，我們已經在目標專業領域建立了完善的體系，並且擁有日益活躍的患者群體。

So I would say a primary driver for growth over the course of this year is really that activated prescriber base and our ability to both grow and expand that as well as deepen it over time. Our chart shows -- we understand very well the dynamics of how a first patient starts and then a positive experience leads to growth and deepening over time.

因此，我想說，今年成長的主要動力實際上是活躍的處方者基礎，以及我們隨著時間的推移發展、擴大和深化這一基礎的能力。我們的圖表顯示——我們非常了解第一位患者如何開始治療，然後積極的體驗如何隨著時間的推移而導致患者病情的成長和深化。

Secondly, we see more and more patients coming in and asking about AYVAKIT, showing that our direct to patient efforts are really working and we expect this to also capitalize growth over the course of this year. As we shift into the newer specialties, we think this will enable us to further amplify these efforts.

其次，我們看到越來越多的患者前來詢問 AYVAKIT，這表明我們直接面向患者的努力確實有效，我們預計這也會在今年實現成長。隨著我們轉向新的專業，我們認為這將使我們能夠進一步擴大這些努力。

There's really an untapped opportunity of additional SM patients who are being seen by derms and gastros. I think what we've learned from this market is hemocs alone are only about a third of the opportunities. So we know it's important to expand.

皮膚科醫生和胃腸科醫生正在接診更多 SM 患者，這確實是一個尚未開發的機會。我認為我們從這個市場中了解到，單是血液學研究 (hemocs) 只佔了大約三分之一的機會。所以我們知道擴張很重要。

Our objectives with derms and gastros are really the ability to move these patients towards treatment, whether or not they're literally the prescribers at the outset, but they can also refer to our very strong and and growing prescriber base. And we expect this to further catalyze growth really in 2026 and beyond.

我們對皮膚科和胃腸科的目標實際上是讓這些患者接受治療，無論他們一開始是否是處方醫生，但他們也可以參考我們非常強大且不斷增長的處方醫生基礎。我們預計這將在 2026 年及以後進一步促進成長。

So just for clarity, we really do expect our primary prescriber base to be that growing base of allergists. Our stable base of the hemocs group, which sees the minority or the smaller group of patients. And then the growth into GIs and derms will really be 2026.

因此，為了清楚起見，我們確實希望我們的主要處方者群體是不斷增長的過敏症專家群體。我們的 Hemocs 組有穩定的基數，該組的患者為少數或較小群體。而胃腸道和皮膚病學領域的真正增長將在 2026 年實現。

Derek Archila, Wells Fargo.

德里克·阿奇拉，富國銀行。

Hey. Good morning, and thanks for taking the questions. I just want to understand how durable a 10% free drug rate is. And I wonder if you could characterize how the patient adds have trended in April relative to IQ. Thanks.

嘿。早上好，感謝您回答問題。我只是想了解 10% 的免藥率能維持多久。我想知道您是否可以描述一下四月份患者的注意力相對於智商的變化趨勢。謝謝。

So Derek, we don't really talk about the ongoing quarter, but we can certainly talk about how our view of the durability of the free patient goods rate. And just to know, it's actually well below 10% at this point. So Philina, do you want to talk a little bit about how you're thinking about that for the rest of the year, the free goods rate?

因此，德里克，我們實際上並沒有談論當前這個季度，但我們當然可以談談我們對免費患者商品率持久性的看法。需要知道的是，目前這一比例實際上遠低於 10%。那麼菲莉娜，你想談談你對今年剩餘時間的免費商品率的看法嗎？

Yeah. I think what we're really emphasizing is we've de-risked. We've majorly de-risked the variable of free goods by just moving this big base of patients. This large number of patients have been able to access commercial therapy in Q1, and that's been due to the availability of foundation funding, the ability of patients to navigate the new smoothing process.

是的。我認為我們真正強調的是我們已經降低了風險。透過轉移這龐大的患者群體，我們已經大大降低了免費商品的風險。第一季度，如此多的患者能夠接受商業治療，這得益於基金會的資金支持，以及患者能夠適應新的平滑流程。

And so, we also feel like with this type of floor -- well, there's probably not room for this to further improve, but we expect that rate to remain relatively durable over the course of the year. Now, of course, what we'll be watching is as new Medicare patients come on, how able will they be to access commercial therapy, and that depends on factors like how long will foundation funding continue to be available as well.

因此，我們也覺得，對於這種類型的地板，可能沒有進一步改善的空間，但我們預計這一比率在一年內將保持相對持久。現在，當然，我們要關注的是，隨著新的醫療保險患者的加入，他們將如何能夠獲得商業治療，而這也取決於基金會資金將持續提供多長時間等因素。

But I would say, it's the de-risking of the patients who have already moved, which has led to a more favorable than expected upside. That's one of the key factors in our updated guidance range. But really, it's the underlying fundamentals that we expect continued growth in patient starts and patients on therapy that we expect to grow throughout the course of the year.

但我想說，已經轉院的患者的風險降低，帶來了比預期更有利的效益。這是我們更新指導範圍的關鍵因素之一。但實際上，我們預計患者數量和接受治療的患者數量將持續成長，並且預計全年都將保持成長。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Hey. Good morning. This is Mark on for Salveen. Thanks so much for taking our question. You guys mentioned you may show 808 data from the POC studies in Sindu this year. In your view, what is the bar for 808 and Sindu and also in allergic rhinoconjunctivitis, and how do you think this will compare to the antibodies here?

嘿。早安.我是 Salveen 的 Mark。非常感謝您回答我們的問題。你們提到今年可能會展示來自辛度的 POC 研究的 808 個數據。您認為 808 和 Sindu 以及過敏性鼻結膜炎的標準是什麼？您認為這與這裡的抗體相比如何？

Yeah. In terms of the cadence of the data, we're going to need to see how the enrollment goes and there is a relatively rare form of the disease, and we'll update you all as we know more about how the enrollment's going.

是的。就數據的節奏而言，我們需要了解招募情況，並且存在一種相對罕見的疾病形式，我們會在了解更多有關招募情況的信息後向大家通報。

And as I stated earlier in terms of the bar, I think they're going to have to stay tuned to over time to really understand the full efficacy of 808 in these diseases because what we're really trying to do is learn the optimization of the regimen and which symptoms matter most to the patients and how quickly we can resolve these with various testing regimens of 808.

正如我之前提到的，我認為他們必須持續關注才能真正了解 808 在這些疾病中的全部療效，因為我們真正想要做的是了解治療方案的優化以及哪些症狀對患者最重要，以及我們能夠多快地透過 808 的各種測試方案解決這些問題。

I think for the allergic ARC study, again, we're watching enrollment there. The study is up and running and again, we hope to have some data by the end of the year and we'll keep you guys posted on both of those as we continue to execute those programs.

我認為，對於過敏性 ARC 研究，我們正在再次關注其招募情況。這項研究已經開始並正在進行中，我們希望在今年年底前獲得一些數據，並且在我們繼續執行這些計劃時，我們會向你們通報這些數據。

Brian Cheng, JPMorgan.

摩根大通的 Brian Cheng。

Hey, guys. Thanks for taking my question. Can you elaborate a little bit more on the drivers behind the flat growth ex-US this quarter? It's a flat growth there, driven partly by the negotiated price. Thank you.

嘿，大家好。感謝您回答我的問題。您能否進一步闡述本季美國以外地區成長持平的驅動因素？那裡的成長持平，部分原因是協商價格的推動。謝謝。

Thanks, Brian. I think as Christy was mentioning, the underlying fundamental growth in terms of growing patient starts and keeping patients on therapy was exactly where we expected it internationally. As Christy had mentioned, we do get some lumpiness in terms of our distributor markets in particular, and there was some pull forward ordering in those markets in Q4 that really just influenced the dynamics between Q4 and Q1.

謝謝，布萊恩。我認為，正如克里斯蒂所提到的那樣，在增加患者數量和讓患者繼續接受治療方面，潛在的基本成長正是我們在國際上所預期的。正如克里斯蒂所提到的，我們的經銷商市場確實出現了一些波動，第四季度這些市場出現了一些提前訂購的情況，這確實影響了第四季度和第一季之間的動態。

I think what's most important is that the international growth year over year nearly doubled. And as Christie mentioned, we're just in one -- we're just in Germany right now in ISM, and we're going to have more of the larger markets coming in line this year. And so, it's flat from a revenue perspective, it's certainly not flat growth from an underlying fundamental demand perspective.

我認為最重要的是國際成長比去年同期成長了近一倍。正如克里斯蒂所提到的，我們目前只處於德國 ISM 市場，今年我們將有更多更大的市場加入其中。因此，從收入角度來看，它是持平的，但從根本需求角度來看，它肯定不是持平的成長。

Reni Benjamin, Citizens.

雷尼·班傑明（Reni Benjamin），公民。

Hey. Thanks, guys for taking the questions and congratulations on the quarter and the raise of guidance. I'd love to just learn a little bit more about the metrics you guys used to gauge, maybe the success and failure of the DTC advertising strategy. Those tend to be quite costly and I'm curious as to how you evaluate that.

嘿。謝謝大家回答問題，並祝賀本季業績和指導價的提升。我很想進一步了解你們用來衡量 DTC 廣告策略成功與失敗的標準。這些往往相當昂貴，我很好奇你如何評價這一點。

And I think, Philina, you mentioned that there'll be promotional efforts that you're going to employ the dermatologists and gastroenterologists. Wanted to see how big that physician pool was and whether this would increase the total pool of diagnosed patients or that 25,000 that you mentioned already is taking into account the dermatologists and gastroenterologists.

菲莉娜，我想您提到過，您將進行宣傳活動，聘請皮膚科醫生和胃腸病學家。想看看醫生隊伍有多大，以及這是否會增加確診患者的總數，或者您提到的 25,000 已經將皮膚科醫生和胃腸病學家考慮在內。

Yeah. Thanks, Ren. I mean, all DTC is not the same, and we certainly have a more targeted approach here, but Philina, do you want to talk a little bit about what we do from a DTC perspective and then also just the universe of additional specialties we're looking to target.

是的。謝謝，Ren。我的意思是，所有 DTC 都不一樣，我們當然有更有針對性的方法，但 Philina，你想從 DTC 的角度談談我們所做的事情，以及我們希望瞄準的其他專業領域。

Yeah. Absolutely. I would say that our direct to patient efforts are really focused on two things. The first is increasing the awareness of AYVAKIT as a new treatment option, and the second is really creating opportunities for patients to hear from the very positive experiences of other patients who have benefited from AYVAKIT.

是的。絕對地。我想說，我們直接針對患者的努力主要集中在兩件事上。首先是提高人們對 AYVAKIT 作為新治療選擇的認識，其次是真正為患者創造機會，讓他們聽取從 AYVAKIT 中受益的其他患者的非常積極的經驗。

And so, we use a lot of metrics. I think it really comes down to the growth in awareness in AYVAKIT non-users. Obviously, we've seen the number of users increase, but continue to drive the awareness of AYVAKIT using our direct-to-consumer adds.

因此，我們使用了很多指標。我認為這實際上歸因於 AYVAKIT 非用戶意識的提高。顯然，我們看到用戶數量正在增加，但我們仍繼續透過直接面向消費者的廣告來提高 AYVAKIT 的知名度。

We are, I think, importantly, executing on these initiatives in a highly targeted way for this rare disease market. And some of the, I think, most resounding method metrics we've seen is more patients going into offices asking about AYVAKIT as well as the growth that we're seeing in the patients who are starting.

我認為，重要的是，我們針對這個罕見疾病市場以高度針對性的方式實施這些措施。我認為，我們所看到的最顯著的方法指標是，越來越多的患者走進診所詢問 AYVAKIT，我們看到開始使用 AYVAKIT 的患者數量有所增長。

To your question about dermatology and gastroenterology, I would say it's a bit of both things that you mentioned. The first is there's already an untapped opportunity of already diagnosed SM patients being treated by these additional specialties. And secondly, we would actually expect us to grow the treatment rates over time, which can lead to some of that longer term sustained growth.

對於您關於皮膚病學和胃腸病學的問題，我想說您提到的兩者都有一點。首先，已經確診的 SM 患者可以透過這些額外的專科治療獲得尚未開發的機會。其次，我們實際上希望隨著時間的推移提高治療率，這可以帶來一些長期持續的成長。

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Hi. Good morning. Thanks for taking my question. If you think about the different buckets of physicians, the derm and gastros, the allergists and the hemos, can you give us a sense of what's the mix of the patients that are being treated by each specialty and maybe give us a sense of your penetration in terms of region frequency where you are today and then how you see that evolve with this expansion into the germs and gastros data this year. Thank you.

你好。早安.感謝您回答我的問題。如果您考慮不同類別的醫生，皮膚科和胃腸科、過敏症科和血液科，您能否讓我們了解一下每個專業治療的患者組成，並讓我們了解一下您目前在區域頻率方面的滲透率，然後您如何看待今年隨著細菌和胃腸數據的擴展而發生的演變。謝謝。

Philina, do you want to talk a little bit more about specialties?

菲莉娜，你想再多談談特色菜嗎？

Yeah. So I'd say there are a number of SM patients being treated across all of these specialties today. It's our conviction the market opportunity that's really triggering us, I think, to invest in expanding the field force, which enables us to increase reach and frequency across the allergists and hemocs where we've targeted primarily to date as well as expand into the derms and GIs.

是的。所以我想說，今天有許多 SM 患者正在透過所有這些專科接受治療。我認為，正是我們對市場機會的信心促使我們投資擴大現場力量，這使我們能夠增加迄今為止我們主要針對的過敏症和血液病領域的覆蓋面和頻率，並擴展到皮膚科和胃腸道領域。

I would say there's incredible headroom across all of these specialties to continue the growth. Most of the prescribing to date has of course been in allergist and hemocs. One of the things we've been really pleased to see is that the growth of breadth of prescribing has actually been faster into allergy, and we know this is really important to capture that long term opportunity.

我想說，所有這些專業領域都具有巨大的持續成長空間。到目前為止，大多數處方當然都是由過敏症專家和血液科醫生開出的。我們非常高興地看到，過敏類藥物的處方範圍實際上增長得更快，我們知道這對於抓住長期機會非常重要。

And again, for germs and GIs, we are just getting started, and we know that they are both treating an already diagnosed number of SM patients, but there are also patients coming in who can increase that diagnosis rate. They're presenting with cutaneous mastocytosis in the dermatology offices or things like IBS with some other signal of systemic involvement in the GI office.

再次強調，對於細菌和胃腸道疾病，我們才剛開始，我們知道它們都在治療大量已確診的 SM 患者，但也有患者的到來可以提高診斷率。他們在皮膚科就診時表現出皮膚肥大細胞增生症，或在胃腸道科就診時表現出腸躁症 (IBS) 等症狀以及其他系統性病變的信號。

Maybe one thing I'll just add is that as we think about AYVAKIT, it really is the opportunity that the long term safety data that really lowers the bar as people think about the patients who are most -- who could really benefit from the treatment. And so, we all use these measures of TSF score and we try to classify patients as moderate, mild, severe, all these things, that's really a regulatory tool.

也許我想補充一點，當我們考慮 AYVAKIT 時，它確實是一個機會，長期安全數據確實降低了標準，因為人們會考慮最能從治療中真正受益的患者。因此，我們都使用這些 TSF 評分測量方法，並嘗試將患者分為中度、輕度、重度，所有這些，這實際上是一種監管工具。

And what we see out in clinical care is it's about a patient and whether or not they are well controlled and whether or not they can do the things they want to do, go to work, participate in family events, and what we know is that a lot of patients who cannot across all of these specialties, and that's really the clinical context in a commercial setting that is very different than a context that we need for a regulatory approval.

我們在臨床護理中看到的是，它與患者有關，他們是否得到很好的控制，他們是否可以做他們想做的事情，去工作，參加家庭活動，而我們知道的是，很多患者無法跨越所有這些專業，而這實際上是商業環境中的臨床背景，與我們獲得監管批准所需的背景非常不同。

And so, I think the fact that AYVAKIT is so well tolerated, we have three years now plus data really makes us believe this is the right moment to be continuing to expand an allergy and moving into GI and derms who we know will be very positively receive that that clinical long-term profile.

因此，我認為 AYVAKIT 耐受性如此之好，我們現在已經擁有三年以上的數據，這讓我們相信這是繼續擴大過敏症並進入胃腸道和皮膚科的正確時機，我們知道這些科室將非常積極地接受這種臨床長期概況。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

Hey. Good morning, it's Alex on Peter. Thanks for taking the question. Just a quick one on the new field force you've hired. Could you quantify that relative to the most recent or I guess existing salesforce? Thank you.

嘿。早安，我是 Peter 的 Alex。感謝您回答這個問題。我只想簡單介紹一下您僱用的新現場人員。您能否根據最近的或現有的銷售人員來量化這一點？謝謝。

Philina, do you want to talk about the size increase.

菲莉娜，你想談談尺寸增加的事嗎？

Yeah. So this is an incremental field force expansion that will enable us to both increase our reach and frequency on the current prescriber base as well as to expand to these other specialties. But importantly, we're able to do this in an incredibly targeted way, leveraging the strength of our analytics to know where patients are engaging most frequently across these specialties.

是的。因此，這是一個漸進式的現場力量擴展，它將使我們能夠增加當前處方者基礎的覆蓋範圍和頻率，並擴展到其他專業。但重要的是，我們能夠以非常有針對性的方式做到這一點，利用我們的分析優勢來了解患者在這些專業中最常參與的地方。

I think the key piece underlying all of this is like most of this market we can see resides outside of hematology. And so, this is an important lever for us to continue to drive growth in allergy as well as moving into other specialties.

我認為所有這一切的關鍵在於，我們所看到的這個市場的大部分都存在於血液學之外。因此，這是我們持續推動過敏領域發展以及進軍其他專業領域的重要槓桿。

David Dai, UBS.

瑞銀集團戴維戴（David Dai）。

Great. Thanks for taking my questions. I just wanted to drill down on the prescriber base. Last year, you mentioned that as you're explaining to the dermatologist and the GI prescribers, how should we think about the compliance rate of these patients given that these patients could be moderate symptoms.

偉大的。感謝您回答我的問題。我只是想深入了解處方者的情況。去年，您提到，當您向皮膚科醫生和胃腸病醫生解釋時，考慮到這些患者可能只有中度症狀，我們應該如何考慮這些患者的依從率。

Yeah. That was a little bit to what I was mentioning is that it's the idea of milder symptoms is not really the pull through here, right? In a clinical care setting, it's patients who are just do not have enough control over whatever their symptoms may be to be able to do the things that they want to do in life.

是的。這與我剛才提到的有點相似，即症狀較輕並不能真正起到治療作用，對嗎？在臨床照護環境中，患者無法充分控制自己的症狀，無法做自己想做的事。

And so, really in the commercial context that is the context. It's around is a patient well controlled or not. And so, the rubric of patients being more severe versus less severe across specialties is really not relevant for the commercial setting like it is for a clinical development setting.

所以，實際上在商業環境中這就是背景。關鍵在於病人的病情是否得到良好控制。因此，不同專科中病患病情較重與較輕的標準對於商業環境而言實際上並不像對於臨床開發環境那麼重要。

The only thing I would add to that is that our commercial compliance across the board has been exceptionally high, which I think just speaks to the profile AYVAKIT once the patients makes the decision to start on therapy. We see patients doing really well. They're staying on therapy, they're highly compliant, and they're sticky.

我唯一想補充的是，我們整體的商業合規性一直非常高，我認為這恰恰說明了一旦患者決定開始治療，AYVAKIT 的形象就很好。我們看到病人的狀況非常好。他們堅持接受治療，非常順從，而且很堅持。

Judah Frommer, Morgan Stanley.

猶大‧弗洛默，摩根士丹利。

Hi. Thanks for taking the question. Just to follow up on the urticaria indication for 808. I'd be curious how you're viewing unmet need in (inaudible) and CSU, whether the depicts an approval and CSU affects that, and whether risk benefit profile could be viewed differently by derms versus allergists. Thanks.

你好。感謝您回答這個問題。只是為了跟進 808 的蕁麻疹指徵。我很好奇您如何看待（聽不清楚）和 CSU 中未滿足的需求，這是否描述了批准，而 CSU 是否對此有影響，以及皮膚科醫生和過敏症專家對風險收益概況的看法是否不同。謝謝。

Hi. Yeah. So just first of all, I think that in most of these diseases having a small molecule daily oral solution is really what the patients are looking for. And so, we were pleased to see that (inaudible) had the activity that it did really helping everyone understand that this is a chronic inflammatory disease, but we still believe that addressing the mast cell directly, which is the driver of the disease is the right way to approach it. And that a small molecule will be the preferred solution.

你好。是的。首先，我認為對於大多數此類疾病來說，使用小分子每日口服溶液是患者真正需要的。因此，我們很高興看到（聽不清楚）確實發揮了作用，幫助每個人了解這是一種慢性發炎疾病，但我們仍然相信，直接針對肥大細胞（疾病的驅動因素）才是解決問題的正確方法。小分子將是首選的解決方案。

Sudan Loganathan, Stephens.

蘇丹·洛加納坦，史蒂芬斯。

Hi. Good morning. Thank you for taking my questions and congrats again on the sales results for AYVAKIT. My question is regards on the progress with elenestinib, BLU-808 and go to dominate your first protein degrader programs. Gow's your OpEx spend breakdown between the commercial and development programs prioritized? Is the profitability and free cash flow in the cards potentially this year? Or could we expect any of those earnings from AYVAKIT to be reinvested into the pipeline?

你好。早安.感謝您回答我的問題，並再次恭喜AYVAKIT的銷售表現。我的問題是關於 elenestinib、BLU-808 的進展以及主導您的第一個蛋白質降解劑程序。您的營運支出在商業和開發專案之間的優先順序如何細分？今年有可能實現獲利和自由現金流嗎？或者我們可以預期 AYVAKIT 的任何收益都會被重新投資到管道中？

Mike, so you want to take that.

麥克，所以你想接受這個。

Yeah. This is my thing. So I mean, as we've talked previously like capital allocation and prioritization has been one of our key priorities really over the last couple of years to make sure that we are investing in what we see are the greatest opportunities to drive topline growth both now with AYVAKIT and in the future with pipeline.

是的。這是我的東西。所以我的意思是，正如我們之前談到的，資本配置和優先排序在過去幾年中一直是我們的首要任務之一，以確保我們投資於我們認為最有潛力推動營收成長的機會，無論是現在的 AYVAKIT 還是未來的管道。

And so, we've been really disciplined on both being able to make sure that we're investing appropriately in AYVAKIT but also targeting within our pipeline where we think we have the greatest potential to drive growth.

因此，我們非常嚴格，既能確保對 AYVAKIT 進行適當的投資，又能在我們的管道中鎖定我們認為最有潛力推動成長的領域。

So it's not so much like we're expecting to see modest increases as I mentioned in both SG&A spend and R&D because we'll be investing in both areas to drive again both near-term and long-term growth.

因此，我們並不期望看到我在銷售、一般和行政費用以及研發費用方面出現小幅成長，因為我們將在這兩個領域進行投資，以再次推動短期和長期成長。

And I think, specifically, we don't typically break down like within the pipeline where that program spend is going, but clearly elenestinib and 808 are going to be the top priorities in the year term to drive that.

我認為，具體來說，我們通常不會在專案流程中分解支出的去向，但顯然，elenestinib 和 808 將成為年度內推動這一目標的首要任務。

And one thing I would just add is that I think we have a really good track record here at Blueprint and in terms of our business development strategy. And I think we are very committed to maintaining a durable financial profile, making sure we're sustainable and able to invest in the highest -- prioritize drivers of growth.

我想補充一點，我認為 Blueprint 和我們的業務發展策略都擁有良好的業績記錄。我認為我們非常致力於維持持久的財務狀況，確保我們的永續發展並能夠投資於最優先的成長動力。

And if there are programs that either we believe we would benefit from a partnership in terms of execution and or maybe not are our highest strategic priority, we have a track record of having outlicensed those and for instance, just recently, we put a program in the hands of IDRX and we just received $80 million at the beginning of this year due to that transaction and that was a program that we chose not to move forward ourselves but certainly was beneficial to move forward in someone else's hands.

如果我們認為某些項目在執行方面會從合作中受益，或者可能不是我們的最高戰略重點，我們有將這些項目授權給別人的記錄，例如，就在最近，我們將一個項目交給了 IDRX，由於這筆交易，我們在今年年初獲得了 8000 萬美元，我們自己選擇不推進這個項目，但如果交給別人推進，肯定會有好處。

So we will continue to look at using business development to enable us to first and foremost meet our corporate strategic interests and then secondly to make sure we're maintaining that really sustainable financial profile.

因此，我們將繼續考慮利用業務發展，首先讓我們滿足企業策略利益，其次確保我們保持真正可持續的財務狀況。

Thank you. That's all the questions we have time for today. Kate Haviland, I would send the call back over to you.

謝謝。這就是我們今天所討論的所有問題。凱特哈維蘭，我會把電話轉給你。

So thank you everybody. We are off to a very strong start here in 2025 with AYVAKIT firmly on the path to realizing its multi billion dollar peak opportunity. We're advancing our pipeline. We have the assets in place. We have the strategy in place to really achieve our goal of fundamentally shifting the way allergic inflammatory diseases are treated by targeting the mast cell. So we thank you all for your continued support of Blueprint Medicines, and we invite you to continue to follow our progress throughout this year.

謝謝大家。2025 年，我們將迎來一個非常強勁的開端，AYVAKIT 將堅定地走在實現數十億美元巔峰機會的道路上。我們正在推進我們的管道。我們已擁有資產。我們已經制定了策略來真正實現我們的目標，即透過針對肥大細胞從根本上改變過敏性發炎疾病的治療方式。因此，我們感謝大家對 Blueprint Medicines 的持續支持，並邀請您在今年繼續關注我們的進展。

Thank you. This concludes today's conference call. You may not disconnect.

謝謝。今天的電話會議到此結束。您不能斷開連線。